Adult neurogenesis and its promise as a hope for brain repair

After the pioneer report by Joseph Altman of adult neurogenesis (AN) in mammals in 1962, the phenomenon of AN was “rediscovered” some 20 years later, first in songbirds and then in mammals. Since the 1990s, interest in AN was fueled by the hope that it could lead to the treatment of neurological deficits by grafting these neurons or their progenitors into brain areas affected by disease or injury. Unfortunately, after 20 years of intense research efforts there is no clear indication that AN can be harnessed for the repair of brain circuits. We argue that the exuberant optimism regarding the potential application of AN for brain repair was misguided by the belief that neurons and their precursors had extensive developmental plasticity. Many of the experiments investigating the potential of AN for brain repair were inspired by the idea that neuronal precursors would be able to adapt, and easily change their developmental fate to replace the lost neurons. However, research during the last 20 years has shown that, in most cases, the fate of neurons is strongly determined and that it rarely changes. Understanding the mechanisms that control neural cell fate may allow for the engineering of adult stem cells so that they can give rise to neurons with properties appropriate for the host circuit to be repaired. The lack of phenotypic flexibility of neuronal progenitors may eventually prove to be advantageous, as this may provide a high degree of predictability (and safety) in the properties of reprogrammed cells. We suggest that AN is still a useful model to understand how neurons integrate into adult brain circuits, and that brain repair will require a thorough understanding of the genetic programs that control neuronal fate and neuronal migration

Lineage does not regulate the connectivity of projection neurons in the mouse olfactory bulb

Lineage regulates the synaptic connections between neurons in some regions of the invertebrate nervous system. In mammals recent experiments suggest that cell lineage determines the connectivity of pyramidal neurons in the neocortex, but the functional relevance of this phenomenon and whether it occurs in other neuronal types remains controversial. We investigated whether lineage plays a role in the connectivity of mitral and tufted cells, the projection neurons in the mouse olfactory bulb. We used transgenic mice to label neuronal progenitors sparsely and observed that clonally related neurons receive synaptic input from olfactory sensory neurons expressing different olfactory receptors. These results indicate that lineage does not determine the connectivity between olfactory sensory neurons and olfactory bulb projection neurons

Lineage does not regulate the sensory synaptic input of projection neurons in the mouse olfactory bulb

Lineage regulates the synaptic connections between neurons in some regions of the invertebrate nervous system. In mammals, recent experiments suggest that cell lineage determines the connectivity of pyramidal neurons in the neocortex, but the functional relevance of this phenomenon and whether it occurs in other neuronal types remains controversial. We investigated whether lineage plays a role in the connectivity of mitral and tufted cells, the projection neurons in the mouse olfactory bulb. We used transgenic mice to sparsely label neuronal progenitors and observed that clonally related neurons receive synaptic input from olfactory sensory neurons expressing different olfactory receptors. These results indicate that lineage does not determine the connectivity between olfactory sensory neurons and olfactory bulb projection neurons

Transplanted neurons form both normal and ectopic projections in the adult brain

Transplantation of embryonic or stem cell derived neurons has been proposed as a potential therapy for several neurological diseases. Previous studies reported that transplanted embryonic neurons extended long‐distance projections through the adult brain exclusively to appropriate targets. We transplanted E14 lateral ganglionic eminence (LGE) and E15 cortical precursors from embryonic mice into the intact adult brain and analyzed the projections formed by transplanted neurons. In contrast to previous studies, we found that transplanted embryonic neurons formed distinct long‐distance projections to both appropriate and ectopic targets. LGE neurons transplanted into the adult striatum formed projections not only to the substantia nigra, a normal target, but also to the claustrum and through all layers of fronto‐orbital cortex, regions that do not normally receive striatal input. In some cases, inappropriate projections outnumbered appropriate projections. To examine the relationship between the donor cells and host brain in establishing the pattern of projections, we transplanted cortical precursors into the adult striatum. Despite their heterotopic location, cortical precursors not only predominantly formed projections appropriate for cortical neurons, but they also formed projections to inappropriate targets. Transplantation of GFP‐expressing cells into β‐galactosidase‐expressing mice confirmed that the axonal projections were not created by the fusion of donor and host cells. These results suggest that repairing the brain using transplantation may be more complicated than previously expected, because exuberant ectopic projections could result in brain dysfunction. Understanding the signals regulating axonal extension in the adult brain will be necessary to harness stem cells or embryonic neurons for effective neuronal‐replacement therapies

Generation of tissue-specific transgenic birds with lentiviral vectors

Birds are of great interest for a variety of research purposes, and effective methods for manipulating the avian genome would greatly accelerate progress in fields that rely on birds as model systems for biological research, such as developmental biology and behavioral neurobiology. Here, we describe a simple and effective method for producing transgenic birds. We used lentiviral vectors to produce transgenic quails that express GFP driven by the human synapsin gene I promoter. Expression of GFP was specific to neurons and consistent across multiple generations. Expression was sufficient to allow visualization of individual axons and dendrites of neurons in vivo by intrinsic GFP fluorescence. Tissue-specific transgene expression at high levels provides a powerful tool for biological research and opens new avenues for genetic manipulation in birds

Monitoring cell-cell contacts in vivo in transgenic animals

We used a synthetic genetic system based on ligand-induced intramembrane proteolysis to monitor cell-cell contacts in animals. Upon ligand-receptor interaction in sites of cell-cell contact, the transmembrane domain of an engineered receptor is cleaved by intramembrane proteolysis and releases a protein fragment that regulates transcription in the interacting partners. We demonstrate that the system can be used to regulate gene expression between interacting cells, both in vitro and in vivo, in transgenic Drosophila We show that the system allows for detection of interactions between neurons and glia in the Drosophila nervous system. In addition, we observed that when the ligand is expressed in subsets of neurons with a restricted localization in the brain it leads to activation of transcription in a selected set of glial cells that interact with those neurons. This system will be useful to monitor cell-cell interactions in animals, and can be used to genetically manipulate cells that interact with one another

Sex differences in the use of spatial cues in two avian brood parasites

Shiny and screaming cowbirds are avian interspecific brood parasites that locate and prospect host nests in daylight and return from one to several days later to lay an egg during the pre-dawn twilight. Thus, during nest location and prospecting, both location information and visual features are available, but the latter become less salient in the low-light conditions when the nests are visited for laying. This raises the question of how these different sources of information interact, and whether this reflects different behavioural specializations across sexes. Differences are expected, because in shiny cowbirds, females act alone, but in screaming cowbirds, both sexes make exploratory and laying nest visits together. We trained females and males of shiny and screaming cowbird to locate a food source signalled by both colour and position (cues associated), and evaluated performance after displacing the colour cue to make it misleading (cues dissociated). There were no sex or species differences in acquisition performance while the cues were associated. When the colour cue was relocated, individuals of both sexes and species located the food source making fewer visits to non-baited wells than expected by chance, indicating that they all retained the position as an informative cue. In this phase, however, shiny cowbird females, but not screaming, outperformed conspecific males, visiting fewer non-baited wells before finding the food location and making straighter paths in the search. These results are consistent with a greater reliance on spatial memory, as expected from the shiny cowbird female’s specialization on nest location behaviour.Fil: Lois Milevicich, Jimena. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Kacelnik, Alex. University of Oxford; Reino UnidoFil: Reboreda, Juan Carlos. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

Lectura y bienestar: promoción y animación inclusiva a la lectura

En  el  marco  del  Programa  APEX,  Universidad  de  la  República  – Uruguay,  desde  su  Subprograma  Infancia-Animación  Sociocultural  y Recreación el proyecto “Con Voz(s) Cuento” propone la edición de audiolibros accesibles con el objetivo de: Contribuir a motivar y potenciar  el  hábito  de  la  lectura  y  el  acercamiento  tanto  al libro como  a  otros  formatos  o  soportes  con  la  producción  de material  de  audio  y formatos  accesibles  para  personas  con discapacidad  visual  y  otras  discapacidades.  Se  desarrollan actividades  integradas,  intergeneracionales  y  entre  pares, vinculadas  a  transitar  por  los  orígenes  y  la evolución  de  la escritura,  el  libro,  la  biblioteca  y  el  valor  inclusivo  de  las TIC desde un pasaje lúdico-expresivo con el fin de contribuir al acceso  de  personas  con  discapacidad  visual  a  los  bienes culturales promoviendo una mayor autonomía e inclusión social.    Palabras  clave:  Lectura;  discapacidad;  accesibilidad  TIC; bienestar.    Abstract: Under  the  APEX  Program,  University  of  the  Republic  -  Uruguay, since  its  Sub  Sociocultural  Children-Animation  and  Recreation project  "With  Voice  (s)  Tale"  offers  editing  accessible audiobooks  in  order  to: Contribute  to  motivate  and  empower  the reading habits and approach both to the book and to other formats or  supports  the  production  of  audio  material  and  accessible formats  for  people  with  visual impairments  and  other disabilities.  integrated,  inter-generational  and  peer  activities linked  to  transit  through  the  origins  and  evolution  of  writing, the  book,  the  library  and  the  inclusive  value  of  ICT  are developed from a fun-expressive passage in order to contribute to the  access  of  people  visually  impaired  to  cultural  property  by promoting greater autonomy and social inclusion.    Keywords: Reading; disability; ICT accessibility; wellness

Persistence of neuronal representations through time and damage in the hippocampus

How do neurons encode long-term memories? Bilateral imaging of neuronal activity in the mouse hippocampus reveals that, from one day to the next, ~40% of neurons change their responsiveness to cues, but thereafter only 1% of cells change per day. Despite these changes, neuronal responses are resilient to a lack of exposure to a previously completed task or to hippocampus lesions. Unlike individual neurons, the responses of which change after a few days, groups of neurons with inter- and intrahemispheric synchronous activity show stable responses for several weeks. The likelihood that a neuron maintains its responsiveness across days is proportional to the number of neurons with which its activity is synchronous. Information stored in individual neurons is relatively labile, but it can be reliably stored in networks of synchronously active neurons

Lectura y bienestar: promoción y animación inclusiva a la lectura

Under  the  APEX  Program,  University  of  the  Republic  -  Uruguay, since  its  Sub  Sociocultural  Children-Animation  and  Recreation project  "With  Voice  (s)  Tale"  offers  editing  accessible audiobooks  in  order  to: Contribute  to  motivate  and  empower  the reading habits and approach both to the book and to other formats or  supports  the  production  of  audio  material  and  accessible formats  for  people  with  visual impairments  and  other disabilities.  integrated,  inter-generational  and  peer  activities linked  to  transit  through  the  origins  and  evolution  of  writing, the  book,  the  library  and  the  inclusive  value  of  ICT  are developed from a fun-expressive passage in order to contribute to the  access  of  people  visually  impaired  to  cultural  property  by promoting greater autonomy and social inclusion. En  el  marco  del  Programa  APEX,  Universidad  de  la  República  – Uruguay,  desde  su  Subprograma  Infancia-Animación  Sociocultural  y Recreación el proyecto “Con Voz(s) Cuento” propone la edición de audiolibros accesibles con el objetivo de: Contribuir a motivar y potenciar  el  hábito  de  la  lectura  y  el  acercamiento  tanto  al libro como  a  otros  formatos  o  soportes  con  la  producción  de material  de  audio  y formatos  accesibles  para  personas  con discapacidad  visual  y  otras  discapacidades.  Se  desarrollan actividades  integradas,  intergeneracionales  y  entre  pares, vinculadas  a  transitar  por  los  orígenes  y  la evolución  de  la escritura,  el  libro,  la  biblioteca  y  el  valor  inclusivo  de  las TIC desde un pasaje lúdico-expresivo con el fin de contribuir al acceso  de  personas  con  discapacidad  visual  a  los  bienes culturales promoviendo una mayor autonomía e inclusión social